title: MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K.
abstract: The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3'-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.forename: Huajiang
authors.initials: H
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Jianxi
authors.initials: J
authors.lastname: Wang
authors.forename: Xianye
authors.initials: X
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D019295:Computational Biology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000166:cytology*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008156:Luciferases; D035683:MicroRNAs / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D013778:Tetrazolium Salts; D013844:Thiazoles; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; C022616:thiazolyl blue